Prenatal tobacco and tobacco-cannabis co-exposure: Relationship with attention and memory in middle childhood.

We examined associations between prenatal tobacco exposure (with and without cannabis exposure) and children's performance on laboratory measures of sustained attention, attentional set shifting, and working memory in middle childhood (9-12 years of child age). Participants were recruited in the first trimester of pregnancy and oversampled for prenatal tobacco exposure; with a smaller sample (n = 133; n = 34 non-substance exposed, n = 37 exposed to tobacco only, n = 62 co-exposed) invited (oversampled for co-exposure) to participate in the middle-childhood assessment (M age = 10.6, SD = 0.77; 68% Black, 20% Hispanic). Results for sustained attention indicated lower attention (percent hits) at the first epoch for tobacco only exposed compared to non-exposed and co-exposed; a trend (p = .07) towards increases in impulsive responding across time (a total of 8 epochs) for tobacco exposed (with and without cannabis) compared to non-exposed children; and a significant association between higher number of cigarettes in the first trimester and greater increases in impulsive responding across epochs. However, children prenatally exposed to tobacco (with and without cannabis) demonstrated greater short-term memory compared to children not prenatally exposed, and this difference was driven by higher scores for children prenatally co-exposed to tobacco and cannabis compared to those who were non-exposed. Overall, results suggest that prenatal tobacco exposure, especially in the first trimester, may increase risk for impulsive responding on tasks requiring sustained attention, and that co-use of cannabis did not exacerbate these associations. The higher short-term memory scores among children who were co-exposed compared to non-exposed are perplexing and need replication, particularly in studies with larger sample sizes and samples exposed only to cannabis to examine this more closely.

Subthalamic nucleus deep brain stimulation and impulsivity in Parkinson's disease: a descriptive review.

Standard treatment of Parkinson's disease involves the dopaminergic medications. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an important neurosurgical intervention often used as alternative treatment to drug therapy; however, it can be associated with increase of impulsive behaviors. This descriptive review focused on studies investigating the correlation between Deep brain stimulation of the subthalamic nucleus and impulsivity in Parkinson's disease patients, arguing, the action's mechanism and the specific role of the subthalamic nucleus. We searched on PubMed and Web of Science databases and screening references of included studies and review articles for additional citations. From initial 106 studies, only 15 met the search criteria. Parkinson's Disease patients with and without Deep Brain Stimulation were compared with healthy controls, through 16 different tasks that assessed some aspects of impulsivity. Both Deep brain stimulation of the subthalamic nucleus and medication were associated with impulsive behavior and influenced decision-making processes. Moreover, findings demonstrated that: Impulse Control Disorders (ICDs) occurred soon after surgery, while, in pharmacological treatment, they appeared mainly after the initiation of treatment or the increase in dosage, especially with dopamine agonists. The subthalamic nucleus plays a part in the fronto-striato-thalamic-cortical loops mediating motor, cognitive, and emotional functions: this could explain the role of the Deep Brain Stimulation in behavior modulation in Parkinson's Disease patients. Indeed, increase impulsivity has been reported also after deep brain stimulation of the subthalamic nucleus independently by dopaminergic medication status.

Complementary effects of pine bark extract supplementation on inattention, impulsivity, and antioxidative status in children with attention-deficit hyperactivity disorder: A double-blinded randomized placebo-controlled cross-over study.

The purpose of this study was to investigate the complementary effects of polyphenolic compounds from pine bark extract (PE) as a strong antioxidative substrate on the symptoms of inattention and impulsivity in children with attention-deficit hyperactivity disorder (ADHD). This was a randomized, double-blind, crossover, placebo-controlled study that included two experimental units (4 weeks with PE supplementation and 4 weeks with placebo supplementation) separated by a 2-week washout period. ADHD participants were supplemented with 25 mg or 50 mg PE. We recruited 20 participants (17 boys and 3 girls) with a mean age of 10.0 ± 2.1 years. PE supplementation caused a significant reduction in the inattention and hyperactivity-impulsivity items of SNAP-IV. During the period of PE supplementation, the item of commissions in the Continuous Performance Test III (CPT III) significantly decreased, which was used to evaluate the symptoms of inattention and impulsivity. In addition, the erythrocytic reduced glutathione/oxidized glutathione ratio significantly increased, and the plasma TBARs level significantly decreased after 4 weeks of PE supplementation. However, there was no significant correlation between CPT III (commission) and antioxidative status indictors. PE supplementation may have potential effects of ameliorating inattention and impulsivity, and elevating the antioxidative status in children with ADHD.

Daily, but not occasional, cannabis use is selectively associated with more impulsive delay discounting and hyperactive ADHD symptoms in binge-drinking young adults.

RATIONALE: There is increasing interest in and evidence for the negative impacts of cannabis use in cognitive performance and symptoms of attention-deficit/hyperactivity disorder (ADHD), with age of first cannabis use as a potential amplifier of these associations. However, the existing literature is inconsistent, which may be due to methodological limitations, including small sample sizes. OBJECTIVE: To examine current cannabis use and age of first cannabis use in relation to neurocognitive task performance and ADHD symptoms in a large sample of binge-drinking young adults. METHODS: Participants were young adults (N=730, M age=21.44, 52.6% female) assessed for current cannabis use, neurocognitive task performance, and ADHD symptoms. Three-group ANCOVAs compared individuals reporting frequent (daily/multiple times daily), occasional (weekly/monthly), or no cannabis use. RESULTS: Covarying alcohol use, tobacco use, age, sex, income, and education, daily cannabis users exhibited significantly more impulsive delay discounting and hyperactive-impulsive ADHD symptoms compared to both other groups. However, cannabis use was not associated with inattentive ADHD symptoms, verbal intelligence, working memory, probability discounting, short-term verbal memory, or behavioral inhibition. Age of initiation of cannabis use exhibited neither main effects nor interactions in relation to any domains of cognitive performance or ADHD symptomatology. CONCLUSIONS: The current findings provide support for a link between cannabis use in relation to immediate reward preference and symptoms of hyperactive-impulsive ADHD in young adults, but only among frequent users. No other neurocognitive domains exhibited associations with cannabis and age of first use was neither independently nor interactively associated with cognitive outcomes.

Sex differences in nicotine-induced impulsivity and its reversal with bupropion in rats.

BACKGROUND: Enhancement in cognitive impulsivity and the resulting alterations in decision making serve as a contributing factor for the development and maintenance of substance-use disorders. Nicotine-induced increases in impulsivity has been previously reported in male humans and rodents. Although the potential for sex differences in nicotine-induced impulsivity has not been examined. AIMS AND METHODS: In the present study, male and female Sprague Dawley rats were submitted to a delay discounting task, in which several consecutive measures of self-control were taken. Firstly, rats were tested with vehicle, and next with nicotine doses of 0.4 and 0.8 mg/kg. Thereafter, chronic treatment with bupropion started, and the animals were tested again. Half the animals continued to receive 0.8 mg/kg of nicotine, while the rest received nicotine and also a daily dose of 30 mg/kg of bupropion. RESULTS: When the animals were first tested with nicotine, female rats showed a significant nicotine dose dependent increase of impulsive behaviour, whereas male rats only showed a decrease on their elections of the larger but delayed reward under the highest dose of 0.8 mg/kg of nicotine. Treatment with bupropion blocked the effect of nicotine on decision making in female rats, as they showed results close to their baseline levels. On the other hand, bupropion did not affect the nicotine-induced delay discounting in male rats. CONCLUSION: These findings demonstrate sexually dimorphic effects of nicotine on cognitive impulsivity which may help to shed light on nicotine use vulnerabilities observed in women.

Galantamine improves enhanced impulsivity, impairments of attention and long-term potentiation induced by prenatal nicotine exposure to mice.

Prenatal nicotine exposure (PNE) causes behavioral abnormalities in offspring, such as an enhancement of impulsivity and decrease in attention at adolescence. Here we examined the effects of galantamine (GAL) on the behavioral and electrophysiological changes induced by PNE in mice. Pregnant C57BL/6J mice were exposed to nicotine (0.2 mg/mL) dissolved in sweetened (2% saccharin) drinking water during gestational day 14 and perinatal day 0 (P0). At the ages of postnatal days 42-49 (P42-P49), female offspring displayed impulsivity in the cliff avoidance test and impairment of visual attention in the object-based attention test. Decrease of long-term potentiation (LTP) and extracellular glutamate levels were observed in the prefrontal cortex of PNE mice. Systemic treatment with GAL (1 mg/kg, s.c.), an allosteric potentiating ligand for the nicotinic acetylcholine receptor (nAChR) and a weak cholinesterase inhibitor, attenuated the enhancement of impulsivity and impairment of attention induced by PNE in mice. Further, GAL reversed the impairment of LTP induced by PNE in the prefrontal cortex of mice, although it failed to attenuate the decrease of extracellular glutamate levels. The effects of GAL were blocked by an α 7 nAChR antagonist, methyllycaconitine (1 mg/kg, i.p.). These results suggest that PNE during cortex development affects nicotinic cholinergic-dependent plasticity and formation of impulsivity and attention. Furthermore, GAL could be a useful drug for cognitive impairments-related to attention deficit hyperactivity disorder.

Disentangling the effects of cannabis and cigarette smoking on impulsivity.

BACKGROUND: Cannabis smoking and cigarette smoking often co-occur, yet limited research has investigated the potentially different role impulsivity may play when these behaviours occur in isolation, compared with in combination. AIMS: This study examined trait and behavioural impulsivity as a function of both cigarette and cannabis smoking. METHODS: Trait impulsivity (BIS-11) was compared between 44 non-smokers, 76 cigarette only, 47 cannabis only and 58 cannabis plus cigarette smokers. The effects of cigarette and cannabis smoking on behavioural impulsivity (stop-signal and information sampling tasks) were then assessed in 87 of these participants during a laboratory session. RESULTS: Trait impulsivity was significantly higher in cigarette smokers than non-smokers, irrespective of cannabis use, except for motor impulsivity, where cigarette smoking was only associated with elevated trait impulsivity in non-smokers of cannabis. Dimensions of trait impulsivity were significantly positively related to cigarette smoking frequency and nicotine dependence, but not to cannabis smoking frequency or dependence. Smoking cigarettes or cannabis was associated with significantly impaired reflection impulsivity relative to not smoking either substance. However, no additional increases in reflection impulsivity were observed in those who smoked both cigarettes and cannabis. No group differences in response inhibition were detected. CONCLUSIONS: Heightened trait impulsivity appears to be uniquely related to cigarette smoking, whilst the smoking of cigarettes or cannabis is associated with impairments in reflection impulsivity. Improved outcomes for treating cannabis dependence may result from encouraging concomitant cigarette smokers to cease using both drugs simultaneously in order to reduce heightened impulsivity and risk of relapse.

Pharmacological challenges examining the underlying mechanism of altered response inhibition and attention due to circadian disruption in adult Long-Evans rats.

Endogenous circadian rhythms govern behavior and physiology, while circadian disruption is an environmental factor that impacts cognition by altering the circadian clock at a molecular level. We modeled the effects of 2 sources of circadian disruption - activity occurring during typical rest periods and untimely light exposure - to evaluate the effects of circadian disruption on behavior and underlying neurochemistry. Firstly, adult Long-Evans rats of both sexes were maintained on a 12 h:12 h light:dark cycle and tested using a 5-choice serial reaction time task (5-CSRTT) under 3 conditions: 4 h into the dark phase with no exposure to ambient light during testing (control), 4 h into the dark phase with exposure to ambient light during testing, and 4 h into the light phase. Both models resulted in impulsive behavior and reduced attention compared to control. We established that changes in the diurnal expression pattern occur in the clock gene Period 2 (Per2) in the light phase-tested model. Choline acetyltransferase (Chat) and Dopamine receptor 1 (Drd1) showed rhythmic expression with peak expression during the dark phase regardless of light-testing condition. Next, we performed drug challenges in a new rat cohort to examine the interaction between the cholinergic and dopaminergic neurotransmitter systems in regulating the behavioral changes caused by circadian disruption. We administered the cholinergic agonist nicotine and either the dopamine-1 receptor (DR1) antagonist SCH23390 or the DR2 antagonist eticlopride under the 3 circadian conditions to identify differential drug responses between treatment groups. Rats in both models demonstrated increased sensitivity to nicotine as compared to control, while SCH23390 and eticlopride ameliorated the effect of nicotine on 5-CSRTT performance in both models. Our study is the first to identify detrimental effects of both models of circadian disruption on impulsive behavior, and that the effects of circadian disruption are mediated by an interaction between cholinergic and dopaminergic systems.

Guanfacine treatment improves ADHD phenotypes of impulsivity and hyperactivity in a neurofibromatosis type 1 mouse model.

BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a mutation in one copy of the neurofibromin gene (NF1+/-). Even though approximately 40-60% of children with NF1 meet the criteria for attention deficit hyperactivity disorder (ADHD), very few preclinical studies, if any, have investigated alterations in impulsivity and risk-taking behavior. Mice with deletion of a single NF1 gene (Nf1+/-) recapitulate many of the phenotypes of NF1 patients. METHODS: We compared wild-type (WT) and Nf1+/- mouse strains to investigate differences in impulsivity and hyperactivity using the delay discounting task (DDT), cliff avoidance reaction (CAR) test, and open field. We also investigated whether treatment with the clinically effective alpha-2A adrenergic receptor agonist, guanfacine (0.3 mg/kg, i.p.), would reverse deficits observed in behavioral inhibition. RESULTS: Nf1+/- mice chose a higher percentage of smaller rewards when both 10- and 20-s delays were administered compared to WT mice, suggesting Nf1+/- mice are more impulsive. When treated with guanfacine (0.3 mg/kg, i.p.), Nf1+/- mice exhibited decreased impulsive choice by waiting for the larger, delayed reward. Nf1+/- mice also exhibited deficits in behavioral inhibition compared to WT mice in the CAR test by repetitively entering the outer edge of the platform where they risk falling. Treatment with guanfacine ameliorated these deficits. In addition, Nf1+/- mice exhibited hyperactivity as increased distance was traveled compared to WT controls in the open field. This hyperactivity in Nf1+/- mice was reduced with guanfacine pre-treatment. CONCLUSIONS: Overall, our study confirms that Nf1+/- mice exhibit deficits in behavioral inhibition in multiple contexts, a key feature of ADHD, and can be used as a model system to identify alterations in neural circuitry associated with symptoms of ADHD in children with NF1.

A cross-sectional follow-up study of physical morbidities, neurocognitive function, and attention problems in post-treatment childhood acute lymphoblastic leukemia survivors.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. While ALL therapies are highly effective, western studies have shown excesses late life effects of therapies in survivors. In this survey, we recruited subjects being diagnosed as ALL before the age of 18-year-old and had been in complete continuous remission for at least 3 years. Subjects were arranged to receive three cognitive tests (Wechsler intelligence test, Conners' continuous performance test, and Wisconsin card sorting test). Standardized questionnaires were used to inquiry about attention problem in real life context. Treatment outcome were compared between the standard risk and high/very high risk groups. Final survivors were 42 subjects (26 males, 16 females) with median current age of 17.8 years. Subjects were diagnosed to be with ALL at a median age of 4.8 years. The median survival time (from discontinuation of ALL treatment to the study date) was 8.4 years. Results indicated that 17 subjects (40.5%) had chronic physical conditions in need of clinical management and six subjects (14.3%) had mental condition. For the performance-based cognitive outcome, the average full scale intelligence quotient was 91.7 ± 13.8. Ten percent of the subjects had problem in test of attention, 20% had problem in test of impulsivity and 42.8% of the subject had problems in executive function. When judged from real life contexts, 19 subjects (42%) were with obvious attention problems. Group comparison between standard risk vs high/very high risk patients revealed no difference in neurocognitive outcomes. We hope that this information may benefit the implementation of follow-up program for Taiwanese pediatric leukemia survivors.

Caffeine and cannabinoid receptors modulate impulsive behavior in an animal model of attentional deficit and hyperactivity disorder.

Attention deficit and hyperactivity disorder (ADHD) is characterized by impaired levels of hyperactivity, impulsivity, and inattention. Adenosine and endocannabinoid systems tightly interact in the modulation of dopamine signaling, involved in the neurobiology of ADHD. In this study, we evaluated the modulating effects of the cannabinoid and adenosine systems in a tolerance to delay of reward task using the most widely used animal model of ADHD. Spontaneous Hypertensive Rats (SHR) and Wistar-Kyoto rats were treated chronically or acutely with caffeine, a non-selective adenosine receptor antagonist, or acutely with a cannabinoid agonist (WIN55212-2, WIN) or antagonist (AM251). Subsequently, animals were tested in the tolerance to delay of reward task, in which they had to choose between a small, but immediate, or a large, but delayed, reward. Treatment with WIN decreased, whereas treatment with AM251 increased the choices of the large reward, selectively in SHR rats, indicating a CB1 receptor-mediated increase in impulsive behavior. An acute pre-treatment with caffeine blocked WIN effects. Conversely, a chronic treatment with caffeine increased the impulsive phenotype and potentiated the WIN effects. The results indicate that both cannabinoid and adenosine receptors modulate impulsive behavior in SHR: the antagonism of cannabinoid receptors might be effective in reducing impulsive symptoms present in ADHD; in addition, caffeine showed the opposite effects on impulsive behavior depending on the length of treatment. These observations are of particular importance to consider when therapeutic manipulation of CB1 receptors is applied to ADHD patients who consume coffee.

Na+, K+-ATPase inhibition causes hyperactivity and impulsivity in mice via dopamine D2 receptor-mediated mechanism.

Hyperactivity and impulsivity are common symptoms in several psychiatric disorders. Although dysfunction of Na+, K+-ATPase has been reported to be associated with the psychiatric disorders, it is not clear whether inhibition of Na+, K+-ATPase causes behavioral effects, including hyperactivity and impulsivity, in mice. Here, we evaluated the effect of intracerebroventricular (icv) injection of ouabain, an inhibitor of Na+, K+-ATPase, on hyperactivity and impulsivity in mice. At seven days after icv injection, ouabain-injected mice displayed the increase in the distance traveled in the open field arena in the open field test and the increase in the number of head-dipping behavior in the cliff avoidance test. Chlorpromazine or haloperidol, typical antipsychotics, reduced the hyperactivity and impulsivity in ouabain-injected mice. On the other hand, neither lithium carbonate nor valproate, established mood-stabilizing drugs, improved hyperactivity and impulsivity in our mouse model. Furthermore, ouabain-injected mice exhibited the increase in the number of c-fos-positive cells in the nucleus accumbens and the prefrontal cortex but not in the ventral tegmental area, which was reduced by haloperidol. These results suggest that the dysfunction of Na+, K+-ATPase causes hyperactivity and impulsivity via hyperactivation of dopamine D2 receptor-mediated signaling pathway, causing disturbed neuronal circuits in mice.

Kappa opioid receptors mediate yohimbine-induced increases in impulsivity in the 5-choice serial reaction time task.

Dynorphin (DYN), and its receptor, the kappa opioid receptor (KOR) are involved in drug seeking and relapse but the mechanisms are poorly understood. One hypothesis is that DYN/KOR activation promotes drug seeking through increased impulsivity, because many stimuli that induce DYN release increase impulsivity. Here, we systematically compare the effects of drugs that activate DYN/KOR on performance on the 5-choice serial reaction time task (5-CSRTT), a test of sustained attention and impulsivity. In Experiment 1, we determined the effects of U50,488 (0, 2.5, 5 mg/kg), yohimbine (0, 1.25, 2.5 mg/kg), and nicotine (0, 0.15, 0.3 mg/kg) on 5-CSRTT performance. In Experiment 2, we determined the effects of alcohol (0, 0.5, 1.0, 1.5 g/kg) on 5-CSRTT performance before and after voluntary, intermittent alcohol exposure. In Experiment 3, we determined the potential role of KOR in the pro-impulsive effects of yohimbine (1.25 mg/kg) and nicotine (0.3 mg/kg) by the prior administration of the KOR antagonist nor-BNI (10 mg/kg). Premature responding, the primary measure of impulsivity, was reduced by U50,488 and alcohol, but these drugs had a general suppressive effect. Yohimbine and nicotine increased premature responding. Yohimbine-, but not nicotine-induced increases in premature responding were blocked by nor-BNI, suggesting that impulsivity induced by yohimbine is KOR dependent. This may suggests a potential role for KOR-mediated increases in impulsivity in yohimbine-induced reinstatement.

Preclinical evidence for combining the 5-HT2C receptor agonist lorcaserin and varenicline as a treatment for nicotine dependence.

Varenicline, a nicotinic acetylcholine receptor partial agonist, is used to treat nicotine dependence. Lorcaserin, a 5-HT2C receptor agonist has been approved in some countries to treat obesity. Based on preclinical and preliminary clinical evidence, lorcaserin may have potential to treat nicotine dependence. These experiments examined in rats the effects of combining varenicline (0.5 or 1 mg/kg) and lorcaserin (0.3, 0.6 and 1 mg/kg) on nicotine self-administration, reinstatement of nicotine seeking, responding for food and impulsive action. Both drugs alone reduced nicotine self-administration. Combining varenicline and 0.6 mg/kg lorcaserin reduced responding to a greater extent than either drug alone. In a relapse model, extinguished nicotine seeking was reinstated by a priming injection of nicotine and nicotine-associated cues. Reinstatement was reduced by varenicline (1 mg/kg) and by lorcaserin (0.3 mg/kg). Combining lorcaserin (0.3 mg/kg) with varenicline (0.5 or 1 mg/kg) reduced reinstatement to a greater degree than either drug alone. Both drugs had minimal effects on responding for food, alone or in combination. In the five-choice serial reaction time test, varenicline (0.5 or 1 mg/kg) increased impulsivity, measured as increased premature responding. This effect was reduced by lorcaserin (0.3 mg/kg). Plasma levels of varenicline or lorcaserin were not altered by co-administration of the other drug. Varenicline and lorcaserin have additive effects on nicotine self-administration, and on nicotine seeking. Lorcaserin prevents impulsivity induced by varenicline. This pattern of effects suggests that co-administration of varenicline and lorcaserin has potential as a treatment for nicotine dependence that may exceed the value of either drug alone.

The elevated gradient of aversion: a new apparatus to study the rat behavior dimensions of anxiety, fear, and impulsivity

Few behavioral tests allow measuring several characteristics and most require training, complex analyses, and/or are time-consuming. We present an apparatus based on rat exploratory behavior. Composed of three different environments, it allows the assessment of more than one behavioral characteristic in a short 3-min session. Factorial analyses have defined three behavioral dimensions, which we named Exploration, Impulsivity, and Self-protection. Behaviors composing the Exploration factor were increased by chlordiazepoxide and apomorphine and decreased by pentylenetetrazole. Behaviors composing the Impulsivity factor were increased by chlordiazepoxide, apomorphine, and both acute and chronic imipramine treatments. Behaviors composing the Self-protection factor were decreased by apomorphine. We submitted Wistar rats to the open-field test, the elevated-plus maze, and to the apparatus we are proposing. Measures related to exploratory behavior in all three tests were correlated. Measures composing the factors Impulsivity and Self-protection did not correlate with any measures from the two standard tests. Also, compared with existing impulsivity tests, the one we proposed did not require previous learning, training, or sophisticated analysis. Exploration measures from our test are as easy to obtain as the ones from other standard tests. Thus, we have proposed an apparatus that measured three different behavioral characteristics, was simple and fast, did not require subjects to be submitted to previous learning or training, was sensitive to drug treatments, and did not require sophisticated data analyses.

A Pilot Randomized Controlled Trial to Explore Cognitive and Emotional Effects of Probiotics in Fibromyalgia.

It has recently been found that microbes in the gut may regulate brain processes through the gut microbiota-brain axis, which modulates affection, motivation and higher cognitive functions. According to this finding, the use of probiotics may be a potential treatment to improve physical, psychological and cognitive status in clinical populations with altered microbiota balance such as those with fibromyalgia (FMS). Thus, the aim of the present pilot study with a double-blind, placebo-controlled, randomised design was to test whether a multispecies probiotic may improve cognition, emotional symptoms and functional state in a sample of patients diagnosed with FMS. Pain, impact of FMS, quality of life, anxiety and depressive symptoms were measured during the pre- and post-intervention phases; participants also completed two computerised cognitive tasks to assess impulsive choice and decision-making. Finally, urinary cortisol concentration was determined. To our knowledge, this is the first study that explore the effect of a multispecies probiotic in FMS patients. Our results indicated that probiotics improved impulsivity and decision-making in these patients. However, more research is needed to further explore the potential effects of probiotics on other cognitive functions affected in FMS as well as in other clinical populations.

The factors associated with impulse control behaviors in Parkinson's disease: A 2-year longitudinal retrospective cohort study.

INTRODUCTION: Impulse control behaviors (ICBs) are impulsive-compulsive behaviors often associated with dopamine replacement therapy in Parkinson's disease (PD). Although remission can occur in ICB, only four reports on the ratio of remission and the persistence of ICB have been published, and the associated factors with ICB remission or persistence have been little known. Therefore, we conducted a longitudinal assessment of the remission, persistence, and development of ICB and those associated factors in patients with PD. METHODS: We retrospectively investigated a PD database at Aomori Prefectural Central Hospital, Japan. One hundred and forty-eight patients with PD who could be followed up for 2 years were enrolled. ICB was assessed using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease. Motor severity (Hoehn and Yahr scale and United Parkinson's Disease Rating Scale), cognitive function (Mini-Mental State Examination), and other clinical variables (sex, age, onset age, disease duration, olfactory dysfunction, and dyskinesia) and medications used to treat PD were assessed. Univariate analyses were performed. RESULTS: Seven patients were excluded because of the exclusion criteria, and 141 patients were analyzed. Thirty patients (21.3%) had ICB at baseline, and these patients also had significantly higher use of pergolide. The ICB remission rate was 60%, the ICB persistence ratio was 40%, and the ICB development ratio was 12.6% over 2 years. Statistically, younger age and pergolide use were associated with ICB persistence. Being male, having dyskinesia, and rotigotine, entacapone, zonisamide, and istradefylline use were associated with ICB development. CONCLUSION: This study suggests that younger age and pergolide use may be the new associated factors with ICB persistence and that entacapone, zonisamide, and istradefylline use may be associated with the development of ICB. Drug profiles and medication practices in Japan may explain the association of these factors with ICB.

The effects of cannabidiol on impulsivity and memory during abstinence in cigarette dependent smokers.

Acute nicotine abstinence in cigarette smokers results in deficits in performance on specific cognitive processes, including working memory and impulsivity which are important in relapse. Cannabidiol (CBD), the non-intoxicating cannabinoid found in cannabis, has shown pro-cognitive effects and preliminary evidence has indicated it can reduce the number of cigarettes smoked in dependent smokers. However, the effects of CBD on cognition have never been tested during acute nicotine withdrawal. The present study therefore aimed to investigate if CBD can improve memory and reduce impulsivity during acute tobacco abstinence. Thirty, non-treatment seeking, dependent, cigarette smokers attended two laboratory-based sessions after overnight abstinence, in which they received either 800 mg oral CBD or placebo (PBO), in a randomised order. Abstinence was biologically verified. Participants were assessed on go/no-go, delay discounting, prose recall and N-back (0-back, 1-back, 2-back) tasks. The effects of CBD on delay discounting, prose recall and the N-back (correct responses, maintenance or manipulation) were null, confirmed by a Bayesian analysis, which found evidence for the null hypothesis. Contrary to our predictions, CBD increased commission errors on the go/no-go task. In conclusion, a single 800 mg dose of CBD does not improve verbal or spatial working memory, or impulsivity during tobacco abstinence.

The in Vivo Neurochemical Profile of Selectively Bred High-Responder and Low-Responder Rats Reveals Baseline, Cocaine-Evoked, and Novelty-Evoked Differences in Monoaminergic Systems.

Relative to bred low-responder (bLR) rats, bred high-responder (bHR) rats have an exaggerated locomotor response to a novel environment, take more risks, are more impulsive, and more likely to exhibit compulsive drug-seeking behaviors. These phenotypic differences in addiction-related behaviors and temperament have previously been associated with differences in neurotransmitter signaling, including the mesolimbic dopamine system. In this study, we applied advanced in vivo microdialysis sampling in the nucleus accumbens of bHRs and bLRs to assess differences in basal and stimulated neurochemical efflux more broadly. We used liquid chromatography-mass spectrometry measurements of dialysate samples to quantify a panel of 17 neurochemicals, including dopamine, norepinephrine, serotonin, histamine, glutamate, GABA, acetylcholine, adenosine, DOPAC, 3-MT, HVA, 5-HIAA, normetanephrine, taurine, serine, aspartate, and glycine. We also applied a stable isotope labeling technique to assess absolute baseline concentrations of dopamine and norepinephrine in the nucleus accumbens. Finally, we investigated the role of norepinephrine tone in the nucleus accumbens on the bHR phenotype. Our findings show that bHRs have elevated basal and cocaine-evoked dopamine and norepinephrine levels in the nucleus accumbens compared to those of bLRs. Furthermore, norepinephrine signaling in the nucleus accumbens appeared to be an important contributor to the bHR phenotype because bilateral perfusion of the α1 adrenergic receptor antagonist terazosin (10 µM) into the nucleus accumbens abolished the response of bHRs to novelty. These findings are the first to demonstrate a role for norepinephrine in the bHR phenotype. They reveal a positive relationship between dopamine and norepinephrine signaling in the nucleus accumbens in mediating the exaggerated response to novelty and point to norepinephrine signaling as a potential target in the treatment of impulse control disorders.

N-Acetylcysteine for Nonsuicidal Self-Injurious Behavior in Adolescents: An Open-Label Pilot Study.

BACKGROUND: Nonsuicidal self-injury (NSSI) is common in adolescents and young adults, and few evidence-based treatments are available for this significant problem. N-acetylcysteine (NAC) is a widely available nutritional supplement that has been studied in some psychiatric disorders relevant to NSSI including mood and addictive disorders. This pilot study tested the use of NAC as a potential treatment for NSSI in youth. METHODS: Thirty-five female adolescents and young adults with NSSI aged 13-21 years were enrolled in this study that had an open-label, single-arm study design. All participants were given oral NAC as follows: 600 mg twice daily (weeks 1-2), 1200 mg twice daily (weeks 3-4), and 1800 mg twice daily (weeks 5-8). Patients were seen every 2 weeks throughout the trial, at which time youth reported the frequency of NSSI episodes. Levels of depression, impulsivity, and global psychopathology were measured at baseline and at the end of the trial using the Beck Depression Inventory-II (BDI-II), Barratt Impulsivity Scale, and Symptoms Checklist-90 (SCL-90). RESULTS: About two-thirds of the enrolled female youth completed the trial (24/35). NAC was generally well tolerated in this sample. NAC treatment was associated with a significant decrease in NSSI frequency at visit 6 and visit 8 compared to baseline. We also found that depression scores and global psychopathology scores (but not impulsivity scores) decreased after NAC treatment. Decrease in NSSI was not correlated with decrease in BDI-II or SCL-90 scores, suggesting these might be independent effects. CONCLUSION: We provide preliminary evidence that NAC may have promise as a potential treatment option for adolescents with NSSI. The current results require follow-up with a randomized, placebo-controlled trial to confirm efficacy.